Growth and Colonization of the Intestine by E. coli

性状（由申请方提供）：大肠埃希菌是哺乳动物胃肠道中的主要兼性厌氧菌。然而，E.大肠杆菌在哺乳动物宿主中的定植尚不清楚。根据营养生态位假说，肠道中的众多生态位由营养物质的可利用性定义，物种通过竞争一种或几种限制性营养物质而共存。这一假说表明，Escherosal E.大肠杆菌菌株可能作为抵抗肠道E.大肠杆菌病原体，但它还没有在这方面进行过测试。在这种竞争性的更新申请中，我们建议通过测试粘液源性营养物质提供竞争性大肠杆菌占据的营养小生境的假设，来扩展我们对肠道定植的营养基础的研究。大肠杆菌和致病菌株。第一个具体的目标将测试的假设，不同的E。大肠杆菌和致病菌株优先使用不同的营养物来定殖小鼠肠道。进展报告中描述的工作表明，不同的E。大肠杆菌菌株使用不同的营养物来定殖。对于代表E.大肠杆菌，定殖开始和维持阶段的特定营养需求将通过使用为目前资助的项目制定的策略来确定，即，在设计用于模拟小鼠肠的条件下在DNA阵列上诱导的基因将被敲除，突变体与它们的野生型亲本竞争测试以确定它们对于定殖的相对适合性。第二个具体目标将测试这一假设，即不同营养物质的优先利用和/或转换到替代营养的能力是E.大肠杆菌菌株代表四个系统发育组中的每一个。还将检验推论假设，即对相同营养素的直接竞争导致其中一种菌株的定殖适合度降低。这些研究可能有助于解释人类对大肠杆菌感染易感性的差异。大肠杆菌病原体

DESCRIPTION (provided by applicant): Escherichia coli is the predominant facultative anaerobe in the gastrointestinal tracts of mammals. Yet the essence of how E. coli colonizes its mammalian hosts is not understood. According to the nutrient-niche hypothesis, the numerous ecological niches in the intestine are defined by nutrient availability and species coexist by competing for one or a few limiting nutrients. This hypothesis suggests that commensal E. coli strains might act as a first line of defense against enteric E. coli pathogens, but it has not been tested in that light. In this competing renewal application, we propose to extend our investigation of the nutritional basis for intestinal colonization by testing the hypothesis that mucus-derived nutrients provide nutritional niches occupied by competing E. coli commensal and pathogenic strains. The first specific aim will test the hypothesis that different E. coli commensal and pathogenic strains preferentially use different nutrients for colonization of the mouse intestine. Work described in the progress report suggests that different E. coli strains use different nutrients for colonization. For strains representing the four phylogenetic groups of E. coli, the specific nutrient requirements during the initiation and maintenance stages of colonization will be determined by using strategies developed for the currently funded project, i.e., genes induced on DNA arrays under conditions designed to mimic the mouse intestine will be knocked out and the mutants tested in competition with their wildtype parent to determine their relative fitness for colonization. The second specific aim will test the hypothesis that preferential utilization of different nutrients and/or the ability to switch to alternative nutrition is the basis for co-colonization of E. coli strains representing each of the four phylogenetic groups. The corollary hypothesis will also be tested, that direct competition for the same nutrient leads to decreased fitness for colonization of one of the strains. These studies may help explain differences in human susceptibility to infection by E. coli pathogens.